Suppression of C/EBP α expression in biliary cell differentiation from hepatoblasts during mouse liver development

Background/Aims Intrahepatic biliary cell differentiation takes place in periportal hepatoblasts under the influence of the subjacent mesenchyme, which leads to the suppression of mature hepatocyte marker expression. This study was undertaken to analyze C/EBP α and β expression, which may govern transcription of mature hepatocyte marker genes, during mouse liver development with special attention given to biliary differentiation. Methods Expression of C/EBP α and β was immunohistochemically examined. Expression of α-fetoprotein, albumin and urea cycle enzymes, the genes of which have CCAAT motifs in their upstream regulatory sequences, was examined immunohistochemically or by using in situ hybridization. Results C/EBP α started to be expressed in endodermal cells of 9.5-day liver primordium, and continued to be expressed in hepatoblasts and hepatocytes throughout development. Although biliary cell progenitors transiently expressed mature hepatocyte markers, their expression of C/EBP α was weak or totally absent. The signals of C/EBP β in hepatocytes were weak in fetal liver, but became stronger with postnatal development. Differentiated epithelial cells of intrahepatic biliary structures did not express C/EBP α. Conclusions These data suggest that the suppression of C/EBP α expression may be prerequisite to biliary cell differentiation in the hepatoblast population and one of its earliest signs.